COSMETIC METHOD FOR TREATMENT OF SKIN

Abstract: A method is provided for improving skin condition through a system whose steps include applying to the skin separately on a plurality of days a first composition that incorporates a retinoid which is either retinol or retinoic acid in a pharmaceutically acceptable carrier. Once the skin has acclimated to any irritation induced by the first composition, a second composition is applied to the skin daily for a subsequent period of time. The second composition will also include retinoid but at a level at least 10 % higher than that employed in the first composition. Once the skin has acclimated to the second composition, subsequent progressive increases of the active retinoid can be applied over subsequent periods of time. Finally, a maintenance level composition is utilized with the highest level of retinoid in the progressive program to minimize potential irritation.

Description: COSMETIC METHOD FOR TREATMENT OF SKIN The present invention relates to a cosmetic method for the treatment of skin. In particular it relates to a method for combating the appearance of wrinkles and other signs of aging through a progressive regimen of retinoid skincare. A soft, supple and flexible skin has a marked cosmetic appeal and is an attribute of normal functioning epidermis. As human skin ages with advancing years, the epidermis can become folded, ridged or furrowed to form wrinkles. These signal loss of youthful appearance and herald the transition to old age. Exposure to excessive doses of sunlight accelerates the transition process. Also, the outer layer of the epidermis known as the stratum corneum can become dry and flaky following exposure to cold weather or excessive contact with detergents or solvents. Loss of skin moisture thereby results and the skin begins to lose the soft, supple and flexible characteristics. Emollients such as fats, phospholipids and sterols have in the past been used to soften wrinkled or dry skin. These emollients are only partially effective as a remedy for skin in poor condition. The use of retinoids such as retinol and retinoic acid for enhancing the quality of human skin has been known for some time. There is no doubt that retinoids are therapeutically effective much beyond the common emollients. See U.S. Patent 4,603,146 (Kligman) and U.S. Patent 4,727, 088 (Scott et al.) . While retinoids hold much therapeutic promise, these materials have been found to irritate human skin on repeated topical applications. The irritation may range from a sensation of tingling, itching and burning to clinical signs of redness and peeling. The present invention provides a method for improving skin condition comprising the steps of: (i) applying to the skin separately on a plurality of days a first composition comprising: a retinoid; and a pharmaceutically acceptable carrier,- (ii) applying to the skin, after completion of step (i) , a second composition separately on a plurality of further days comprising: a retinoid identical to but at a concentration at least 10% higher than that employed in step (i) ; and a pharmaceutically acceptable carrier. In a further embodiment the method may further comprise the step (iii) of applying to the skin, after completion of step (ii) , a third composition separately on a plurality of further days comprising: a retinoid, identical to but at a concentration at least 10% higher than that employed in step (ii) ,• and a pharmaceutically acceptable carrier. In a still further embodiment, the invention may additionally comprise the step (iv) of applying to the skin after completion of step (iii) , separately on a plurality of still further days comprising: a retinoid identical to but at a concentration at least 10% higher than that employed in step (iii) ; and a pharmaceutically acceptable carrier,- and step (v) involving maintaining treatment of step (iv) for a period of days whose total is longer than the days in any of steps (i) , (ii) or (iii) , thereby becoming the final step in a progressive program to acclimate skin to any potential irritation imparted by the retinoid. In a further aspect, the invention provides the use of a retinoid in a cosmetic regime to improve skin condition, the regime comprising the steps (i) to (ii) and optionally steps (iii) to (v) as hereinbefore described. Such method of improving skin condition through application of a retinoid in a progressive regime eliminates irritation, especially the sensation of tingling, itching and burning as well as redness and peeling. Fine lines and wrinkles appear visibly reduced; texture, softness and smoothness are dramatically reduced and skin firmness and elasticity become noticeably stronger. The present inventors have now found that intolerance to retinoids can now be overcome through a progressive programme of treatment which allows acclimation to increasing levels of these actives. Preferably the retinoid employed in the compositions according to the invention comprises retinol or retinoic acid. Conveniently, the retinoid is present in an amount of from 0.0001% to 5% by weight of the composition in the first composition, from 0.0002% to 5% by weight of the composition in the second composition, from 0.0003% to 5% by weight of the composition in the third composition and from 0.0004% to 5% by weight of the composition in the fourth composition. Typically, the program is conducted over six weeks. For the first two weeks, a low level of retinoid, which may conveniently be either retinol or retinoic acid, containing first composition is applied to the skin, particularly the face, preferably daily. Levels of the active may suitably range from 0.0001% to 5%, preferably from 0.01% to 0.3%, optimally from 0.02% to 0.2% by weight of the composition. During the third and fourth weeks the treatment is suitably conducted with a second composition containing the ' identical retinoid but at a concentration at least 10% higher than that employed in weeks 1-2. Levels of the active may suitably range from 0.0002% to 5%, preferably from 0.02% to 0.5%, optimally from 0.03% to 0.3% by weight of the composition. Application is again preferably performed on a once-daily basis. In the fifth and sixth weeks, daily treatment is suitably conducted with a third composition containing a retinoid identical to that used in the previous compositions but at a concentration at least 10% higher than in weeks 3-4. Levels of the active may suitably range from 0.0003% to 5%, preferably from 0.03% to 0.8%, optimally from 0.04% to 0.4% by weight of the composition. From the seventh week onward, treatment is suitably conducted with a fourth and final or maintenance composition containing retinoid identical to that employed in the previous compositions but at a concentration at least 10% higher than that present in the third composition. Levels of active may suitably range from 0.0004% to 5%, preferably from 0.04% to 1.2%, optimally from 0.05% to 0.5% by weight of the composition. This final step in the progressive program is suitably conducted daily for at least two months, giving noticeable improvements in skin appearance. Once acclimated by the • starter system of compositions 1-3, the maintenance composition 4 can be applied for any extended length of days. For the purposes of the present invention, the term retinoic acid is intended to include not only the acid form but also salts thereof. Typical salts are the alkalimetal, ammonium and C 2 -C 30 ammonium salts thereof. Particularly preferred are the sodium, potassium, triethanolammonium and ammonium salts. Combinations of all the foregoing may be present in the compositions. Further, the terms "retinol" and "retinoic acid" are intended to include hydrogenated and non-hydrogenated iso erε such as 9-cis-retinol, didehydroretinol, 13-cis-retinoic acid, 13-trans-retinoic acid and didehydroretinoic acid. A wide variety of pharmaceutically acceptable carriers may be utilised for the present invention. Amounts of the carrier may suitably range from 1% to 99.9%, preferably from 80% to 98%, optimally between 90% and 95% by weight of the composition. In a preferred embodiment of the invention, the pharmaceutically acceptable carriers in steps (i) to (iv) are all constituted of identical components in essentially identical concentrations. Preferably, the only variables in formulating the compositions are the concentrations of the retinoid, as well as slight modifications of the major carrier to complement concentration changes on a qs basis. Compositions of the present invention are preferably anhydrous (less than 2% but preferably less than 0.5% water) but may also be aqueous. When water is present, the product form may be as an emulsion in the form of a lotion or cream. Among other types of pharmaceutically acceptable carriers may be silicone oils. Silicone oils may be divided into the volatile and nonvolatile variety. The term "volatile" as used herein refers to those materials which have a measurable vapour pressure at ambient temperature. Volatile silicone oils are preferably chosen from cyclic or linear polydimethylsiloxanes containing from 3 to 9, preferably from 4 to 5, silicon atoms. Linear volatile silicone materials generally have viscosities less than 5 centistokes at 25'C while cyclic materials typically have viscosities of less than 10 centistokes. Examples of preferred volatile silicone oils useful herein include: Dow Corning 344, Dow Corning 345 and Dow Corning 200 (manufactured by Dow Corning Corp.); Silicone 7207 and Silicone 7158 (manufactured by the Union Carbide Corp.); SF 1202 (manufactured by General Electric) ; and SWS-03314 (manufactured by SWS Silicones, Inc.). The nonvolatile silicone oils useful in compositions of this invention are exemplified by the polyalkyl siloxanes, polyalklyaryl siloxanes and polyether siloxane copolymers. The essentially nonvolatile polyalkyl siloxanes useful herein include, for example, polydimethyl siloxanes with viscosities of from 5 to 100,000 centistokes at 25'C. Among the preferred nonvolatile silicones useful in the present compositions are the polydimethyl siloxanes having viscosities from 10 to 400 centistokes at 25°C. Such polyalkyl siloxanes include the Viscasil series (sold by General Electric Company) and the Dow Corning 200 series (sold by Dow Corning Corporation) . Polyalkylaryl siloxanes include poly(methylphenyl) siloxanes having viscosities of from 15 to 65 centistokes at 25°C. ' These are available, for example, as SF 1075 methylphenyl fluid (sold by General Electric Company) and 556 Cosmetic Grade Fluid (sold by Dow Corning Corporation) . Useful polyether siloxane copolymers include, for example, a polyoxyalkylene ether copolymer having a viscosity of 1200 to 1500 centistokes at 25'C. Such a fluid is available as SF-1066 organosilicone surfactant (sold by General Electric Company) . Cetyl dimethicone copolyol and cetyl dimethicone are especially preferred because these materials also function as emulsifiers and emollients. Silicones may suitably be present in amounts ranging from 0.1% up to 60%, preferably from 2% to 25%, optimally between 10% and 20% by weight of the composition. Synthetic esters are a further category of possible pharmaceutically acceptable carriers which can also be utilized as emollients within compositions of the invention. Among the suitable esters are: (1) Alkyl esters of fatty acids having 10 to 20 carbon atoms. Methyl, isopropyl, and butyl esters of fatty acids are useful herein. Examples include hexyl laurate, isohexyl laurate, isohexyl palmitate, isopropyl palmitate, decyl oleate, isodecyl oleate, hexadecyl stearate, decyl stearate, isopropyl isostearate, diisopropyl adipate, diisohexyl adipate, dihexyldecyl adipate, diisopropyl sebacate, lauryl lactate, myristyl lactate, and cetyl lactate. Particularly preferred are C 12 -C 15 alcohol benzoate esters . (2) Alkenyl esters of fatty acids having 10 to 20 carbon atoms. Examples thereof include oleyl myristate, oleyl stearate, and oleyl oleate. (3) Ether-esters such as fatty acid esters of ethoxylated fatty alcohols. (4) Polyhydric alcohol esters. Ethylene glycol mono and di-fatty acid esters, diethylene glycol mono- and di-fatty acid esters, polyethylene glycol (200-6000) mono- and di-fatty acid esters, propylene glycol mono- and di-fatty acid esters, polypropylene glycol 2000 monooleate, polypropylene glycol 2000 monostearate, ethoxylated propylene glycol monostearate, glyceryl mono- and di-fatty acid esters, polyglycerol poly-fatty esters, ethoxylated glyceryl monostearate, 1,3-butylene glycol monostearate, 1,3-butylene glycol diεtearate, polyoxyethylene polyol fatty acid ester, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters are satisfactory polyhydric alcohol esters . (5) Wax esters such as beeswax, spermaceti, myristyl myristate, stearyl stearate. (6) Sterols esters, of which cholesterol fatty acid esters are examples thereof . Fatty alcohols and fatty acids include those compounds having from- 10 to 20 carbon atoms may be utilised as carriers for purposes of the present invention. Especially preferred are such compounds as cetyl, myristyl, palmityl, isostearyl and stearyl alcohols and acids. Surfactants, which are also sometimes designated as emulsifiers, may be incorporated into the cosmetic compositions of the present invention. Surfactants can suitably comprise anywhere from 0.5% to 30%, preferably from 1% to 15% by weight of the total composition. Surfactants may be cationic, nonionic, anionic or amphoteric in nature and combinations thereof may be employed. Illustrative of the nonionic surfactants are alkoxylated compounds based upon fatty alcohols, fatty acids and sorbitan. These materials are available, for instance, from the Shell Chemical Company under the "Neodol" designation. Copolymers of polyoxypropylene- polyoxyethylene, available under the Pluronic trademark sold by the BASF Corporation, are sometimes also useful. Alkyl polyglucosides available from the Henkel Corporation similarly can be utilized for the purposes of this invention. Anionic-type surfactants may include fatty acid soaps, sodium lauryl sulphate, sodium lauryl ether sulphate, alkyl benzene sulphonate, mono and dialkyl acid phosphates and sodium fatty acyl isethionate. Amphoteric surfactants include such materials as dialkylamine oxide and various types of betaines (such as cocoamido propyl betaine) . Another category of functional ingredients within the cosmetic compositions of the present invention are thickeners. A thickener will usually be present in amounts of anywhere from 0.1% to 20% by weight, preferably from 0.5% to 10% by weight of the composition. Exemplary thickeners are cross-linked polyacrylate materials available under the trademark Carbopol from the B.F. Goodrich Company. Gums may be employed such as xanthan, carrageenan, gelatin, karaya, pectin and locust beans gum. Under certain circumstances the thickening function may be accomplished by a material also serving as a silicone or emollient. For instance, silicone gums in excess of 10 centistokes and esters such as glycerol stearate have dual functionality. Skin active agents other than retinoids may also be included in compositions of the present invention. These actives may include sunscreens, tanning agents, anti-acne agents and adjunct anti-wrinkle inhibitors. Among the latter category are ceramides which are N-acylated sphingosine bases. Especially preferred are ceramide l, ceramide 2 and ceramide 3. Identity of these materials are well-outlined in "Advances in Lipid Research, " Vol. 24. pgs. 27-56, by Schurer and Elias (1991). Levels of ceramide may suitably range from 0.00001% to 1% by weight of the composition. Many cosmetic compositions, especially those containing water, must be protected against the growth of potentially harmful microorganisms. Preservatives are, therefore, necessary. Suitable preservatives include alkyl esters of p-hydroxybenzoic acid, hydantoin derivatives, proprionate salts, and a variety of quaternary ammonium compounds. Particularly preferred preservatives are methyl paraben, propyl paraben, imidazolidinyl urea, sodium dehydroxyacetate and benzyl alcohol. Preservatives will usually be employed in amounts ranging from 0.1% to 2% by weight of the composition. Powders may be incorporated into the cosmetic compositions of the invention. These powders include chalk, talc, Fullers earth, kaolin, starch, smectites clays, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, aluminum starch octenyl succinate and mixtures thereof. Other adjunct minor components may also be incorporated into the cosmetic compositions. These ingredients may include colouring agents, opacifiers and perfumes. Amounts of these materials may range anywhere from 0.001% to 20% by weight of the composition. In order that the invention may be well understood, the following examples are given by way of illustration only. All parts, percentages and proportions referred to herein and in the appended claims are by weight unless otherwise indicated. EXAMPLE 1 This example illustrates a treatment system according to the present invention. Daily for two weeks, starter composition 1 is applied to the face. For a subsequent two weeks, starter composition 2 is applied daily to the face. After the fourth week, starter composition 3 is applied daily to the face for a successive two weeks. Finally, maintenance composition 4 is applied daily to the face beginning at the seventh week and continued for at least two months. Components and weight percent concentrations of the aforementioned compositions are outlined in Table I below. TABLE I COMPONENT STARTER COMPOSITION SYSTEM MAINTENANCE (WEIGHT %) COMPOSITION 1 2 3 4 Retinol 0.01 0.025 0.05 0.10 Isostearyl Neopentanoate 36.50 35.01 33.54 32.08 PEG- 8 Caprylic/Capric Glycerides 14.30 14.30 14.30 14.30 Cetyl Octanoate 12.75 12.75 12.75 12.75 Polyglyceryl-6 Dioleate 11.90 11.90 11.90 11.90 Cyclomethicone 10.17 10.17 10.17 10.17 PPG-5-Ceteth-20 5.10 5.10 5.10 5.10 10 Glyceryl Isostearate 3.13 3.13 3.13 3.13 Hydroxycaprylic Acid 0.01 0.01 0.01 0.01 Ceramide 3 0.01 0.01 0.01 0.01 Ceramide 2 0.01 0.01 0.01 0.01 Water qs qs qs qs 15 EXAMPLE 2 This example illustrates another treatment system according to the present invention. Daily for two weeks, starter composition 1 is applied to the face. For a subsequent two weeks, starter composition 2 is applied daily to the face. After the fourth week, starter composition 3 is applied daily to the face for a successive two weeks. Finally, maintenance composition 4 is applied daily to the face beginning at the seventh week and continued for at least two months. Components and weight percent concentrations of the aforementioned compositions are outlined in Table II below. TABLE II COMPONENT STARTER COMPOSITION MAINTENANCE (WEIGHT %) COMPOSITION 1 2 3 Retinoic Acid 0.02 0.08 0.12 Stearic Acid 18.9 18.9 18.9 Isopropyl Myristate 16.3 16.3 16.3 Polyoxyl 40 Stearate 14.2 14.2 14.2 Stearyl Alcohol 10.9 10.9 10.9 Xanthan Gum 0.10 0.10 0.10 Sorbic Acid 0.1 0.1 0.1 Butylated Hydroxytoluene 0.1 0.1 0.1 Water qs qs qs The foregoing examples illustrated only selected embodiments of the present invention and should be considered non-limiting examples with variations and modifications thereof all being within the spirit and purview of this invention.

Claims: CLAIMS 1. A method for improving skin condition comprising the 5 steps of: (i) applying to the skin separately on a plurality of days a first composition comprising: 10 a retinoid; and a pharmaceutically acceptable carrier; and (ii) applying to the skin, after completion of step (i) , a second composition separately on a plurality of 15 further days comprising: a retinoid identical to but at a concentration at least 10% higher than that employed in step (i) ; and a pharmaceutically acceptable carrier. 20 2. A method according to claim 1 further comprising the step of: (iii)applying to the skin, after completion of step (ii) , 25 a third composition separately on a plurality of days comprising: a retinoid identical to but at a concentration at least 10% higher than that employed in step (ii) ,- and 30 a pharmaceutically acceptable carrier. 3. A method for according to claim 2 further comprising the steps of: 35. (iv) applying to the skin, after completion of step (iii) , a fourth composition separately on a plurality of days comprising: a retinoid identical to but at a concentration at least 10% higher than that employed in step (iii) ; and a pharmaceutically acceptable carrier,- (v) maintaining treatment of step (iv) for a period of days whose total is longer than the days in any of steps (i) , (ii) or (iii) , thereby becoming the final step in a progressive program to acclimate skin to any potential irritation imparted by the retinoid. 4. A method according to claim 3 wherein the composition of steps (i) to (iv) have identical components at identical concentrations except that the retinoid concentrations are different among different compositions and that the concentration of the respective pharmaceutically acceptable carriers are accordingly adjusted to accommodate any concentration changes of the retinoid. 5. A method according to any one of claims 1 to 4 wherein the retinoid comprises retinol or retinoic acid. 6. The use of a retinoid in a cosmetic regime to improve skin condition, the regime comprising the steps of: (i) applying to the skin separately on a plurality of days a first composition comprising: a retinoid, and a pharmaceutically acceptable carrier; (ii) applying to the skin, after completion of step (i) , a second composition separately on a plurality of further days comprising: a retinoid identical to but at a concentration at least 10% higher than that employed in step (i) , and a pharmaceutically acceptable carrier; and optionally (iii)applying to the skin, after completion of step (ii) , a third composition separately on a plurality of further days comprising: a retinoid, identical to but at a concentration at least 10% higher than that employed in step (ii) , and a pharmaceutically acceptable carrier; (iv) applying to the skin, after completion of step (iii) , separately on a plurality of still further days comprising: a retinoid identical to but at a concentration at least 10% higher than that employed in step (iii) , and a pharmaceutically acceptable carrier,- and (v) maintaining treatment of step (iv) for a period of days whose total is longer than the days in any of steps (i) , (ii) or (iii) , thereby becoming the final step in a progressive program to acclimate skin to any potential irritation imparted by the retinoid.

Inventors: DOROGI PETER, EVENSON ALAN, MCCOOK JOHN PATRICK, MEYERS ALAN JOEL, DOROGI, PETER, EVENSON, ALAN, MCCOOK, JOHN, PATRICK, MEYERS, ALAN, JOEL
Applicants: UNILEVER NV, UNILEVER PLC, UNILEVER N.V.
Application year: 1994
Main classification: A61K7
IPC codes: A61K8, A61K31, A61P17, A61Q19